scholarly journals Neuronal Intranuclear Inclusion Disease: Longitudinal Case Report of Motor and Nonmotor Symptoms

2019 ◽  
Vol 34 (13) ◽  
pp. 801-805 ◽  
Author(s):  
Jennifer Vermilion ◽  
Mahlon Johnson ◽  
Jayasri Srinivasan ◽  
Jonathan W. Mink
Keyword(s):  
Neurodegenerative Disorder ◽  
Single Case ◽  
Initial Response ◽  
Motor Fluctuations ◽  
Gastrointestinal Dysfunction ◽  
Intranuclear Inclusion ◽  
Nonmotor Symptoms ◽  
Juvenile Parkinsonism ◽  
Neuronal Intranuclear Inclusion ◽  
The University

Neuronal intranuclear inclusion disease is a rare, neurodegenerative disorder with onset in childhood. We report a single case natural history over 10 years and present a review of juvenile parkinsonism and neuronal intranuclear inclusion disease. Our patient was initially seen at the University of Rochester at age 12 years after 4 years of progressive dysarthria, dysphagia, and clumsiness. His neurologic examination was notable for parkinsonism. He had excellent initial response to levodopa, but subsequently developed dopa-induced motor fluctuations, dyskinesias, psychosis, and dystonia. Later in the course, he developed multiple nonmotor symptoms and ultimately died from respiratory failure. Neuropathology demonstrated large eosinophilic nuclear inclusions and small ubiquitin-related modifier 1 (SUMO-1) immunoreactivity, confirming the diagnosis of neuronal intranuclear inclusion disease. This diagnosis should be considered in a patient presenting with juvenile parkinsonism. Clues to the diagnosis include early-onset dopa-induced dyskinesias, gastrointestinal dysfunction, and oculogyric crises.

Long-read sequencing identified repeat expansions in the 5′UTR of the NOTCH2NLC gene from Chinese patients with neuronal intranuclear inclusion disease

2019 ◽  
Vol 56 (11) ◽  
pp. 758-764 ◽  
Author(s):  
Jianwen Deng ◽  
Muliang Gu ◽  
Yu Miao ◽  
Sheng Yao ◽  
Min Zhu ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Electron Microscopic Observation ◽  
Chinese Patients ◽  
Sweat Glands ◽  
Adult Onset ◽  
Intranuclear Inclusion ◽  
Electron Microscopic ◽  
Juvenile Onset ◽  
Long Read ◽  
Neuronal Intranuclear Inclusion

BackgroundNeuronal intranuclear inclusion disease (NIID) is a heterogenous neurodegenerative disorder named after its pathological features. It has long been considered a disease of genetic origin. Recently, the GGC repeated expansion in the 5′-untranslated region (5′UTR) of the NOTCH2NLC gene has been found in adult-onset NIID in Japanese individuals. This study was aimed to investigate the causative mutations of NIID in Chinese patients.MethodsFifteen patients with NIID were identified from five academic neurological centres. Biopsied skin samples were analysed by histological staining, immunostaining and electron microscopic observation. Whole-genome sequencing (WGS) and long-read sequencing (LRS) were initially performed in three patients with NIID. Repeat-primed PCR was conducted to confirm the genetic variations in the three patients and the other 12 cases.ResultsOur patients included 14 adult-onset patients and 1 juvenile-onset patient characterised by degeneration of multiple nervous systems. All patients were identified with intranuclear inclusions in the nuclei of fibroblasts, fat cells and ductal epithelial cells of sweat glands. The WGS failed to find any likely pathogenic variations for NIID. The LRS successfully identified that three patients with adult-onset NIID showed abnormalities of GGC expansion in 5′UTR of the NOTCH2NLC gene. The GGC repeated expansion was further confirmed by repeat-primed PCR in seven familial cases and eight sporadic cases.ConclusionOur findings provided evidence that confirmed the GGC repeated expansion in the 5′UTR of the NOTCH2NLC gene is associated with the pathogenesis of NIID. Additionally, the GGC expansion was not only responsible for adult-onset patients, but also responsible for juvenile-onset patients.

scholarly journals Neuronal intranuclear inclusion disease presented with recurrent vestibular migraine-like attack: a case presentation

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Danhua Zhao ◽  
Sha Zhu ◽  
Qinlan Xu ◽  
Jianwen Deng ◽  
Zhaoxia Wang ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Brain Magnetic Resonance Imaging ◽  
Vestibular Migraine ◽  
Sweat Glands ◽  
Intranuclear Inclusion ◽  
Case Presentation ◽  
Disturbance Of Consciousness ◽  
Corticomedullary Junction ◽  
Electrophysiological Studies ◽  
Neuronal Intranuclear Inclusion

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder characterized by dementia, tremor, episodic encephalopathy and autonomic nervous dysfunction. To date, vestibular migraine (VM)-like attack has never been reported in cases with NIID. Here, we describe an 86-year-old patient with NIID who presented with recurrent vertigo associated with headache for more than 30 years. Case presentation An 86-year-old Chinese woman with vertigo, headache, weakness of limbs, fever, and disturbance of consciousness was admitted to our hospital. She had suffered from recurrent vertigo associated with headache since her 50 s,followed by essential tremor and dementia. On this admission, brain magnetic resonance imaging revealed high intensity signals along the corticomedullary junction on diffusion weighted imaging (DWI). Peripheral neuropathy of the extremities was detected through electrophysiological studies. We diagnosed NIID after detecting eosinophilic intranuclear inclusions in the ductal epithelial cells of sweat glands and identifying an abnormal expansion of 81 GGC repeats in the 5’UTR of NOTCH2NLC gene. Conclusions VM-like attack may be associated with NIID.

scholarly journals NOTCH2NLC CGG Repeats Are Not Expanded and Skin Biopsy Was Negative in an Infantile Patient With Neuronal Intranuclear Inclusion Disease

2020 ◽  
Vol 79 (10) ◽  
pp. 1065-1071
Author(s):  
Ivana Jedlickova ◽  
Anna Pristoupilova ◽  
Helena Hulkova ◽  
Alena Vrbacka ◽  
Viktor Stranecky ◽  
...  
Keyword(s):  
Skin Biopsy ◽  
Neurodegenerative Disorder ◽  
Brain Mri ◽  
Cerebellar Atrophy ◽  
Intranuclear Inclusion ◽  
Negative Results ◽  
Developmental Regression ◽  
Cgg Repeats ◽  
Long Read ◽  
Neuronal Intranuclear Inclusion

Abstract Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder categorized into 3 phenotypic variants: infantile, juvenile, and adult. Four recent reports have linked NIID to CGG expansions in the NOTCH2NLC gene in adult NIID (aNIID) and several juvenile patients. Infantile NIID (iNIID) is an extremely rare neuropediatric condition. We present a 7-year-old male patient with severe progressive neurodegenerative disease that included cerebellar symptoms with cerebellar atrophy on brain MRI, psychomotor developmental regression, pseudobulbar syndrome, and polyneuropathy. The diagnosis of iNIID was established through a postmortem neuropathology work-up. We performed long-read sequencing of the critical NOTCH2NLC repeat motif and found no expansion in the patient. We also re-evaluated an antemortem skin biopsy that was collected when the patient was 2 years and 8 months old and did not identify the intranuclear inclusions. In our report, we highlight that the 2 methods (skin biopsy and CGG expansion testing in NOTCH2NLC) used to identify aNIID patients may provide negative results in iNIID patients.

Neuronal intranuclear inclusion disease and juvenile Parkinsonism

2000 ◽  
Vol 15 (5) ◽  
pp. 990-995 ◽  
Author(s):  
John D. O'Sullivan ◽  
Hasmet A. Hanagasi ◽  
Susan E. Daniel ◽  
Phillip Tidswell ◽  
Stephen W. Davies ◽  
...  
Keyword(s):  
Intranuclear Inclusion ◽  
Juvenile Parkinsonism ◽  
Neuronal Intranuclear Inclusion

scholarly journals Genetic and Pathological Characteristic Patterns of a Family With Neuronal Intranuclear Inclusion Disease

2020 ◽  
Vol 79 (12) ◽  
pp. 1293-1302
Author(s):  
Shugang Zhang ◽  
Qixing Gong ◽  
Di Wu ◽  
Yun Tian ◽  
Lu Shen ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Fragile X ◽  
Cerebrovascular Diseases ◽  
Pathological Examination ◽  
Positive Staining ◽  
Intranuclear Inclusion ◽  
Cgg Repeats ◽  
Genetic Features ◽  
Neuronal Intranuclear Inclusion ◽  
Ataxia Syndrome

Abstract Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disorder. This study aimed to investigate clinical, imaging, genetic, and dermatopathological characteristics of a family with adult-onset NIID. The proband was a 62-year-old woman with 3 brothers and 2 sisters. Of these, 4 had symptoms of paroxysmal visual field defect, extrapyramidal symptoms, dysautonomia, emotional changes, and cognitive dysfunction. Genetic examination revealed no abnormality related to cerebrovascular diseases. More than 200 CGG repeats of FMR1 gene cause fragile X-associated tremor/ataxia syndrome (FXTAS) whereas repeats of the proband were found 29 times, which excluded FXTAS. Quantitative reverse transcription polymerase chain reaction (PCR) and GC-rich-PCR identified an expanded GGC repeat (with ∼100 repeats) in the 5′ region of NOTCH2NLC in the patient and her 2 younger brothers. Pathological examination found eosinophilic intranuclear inclusions inside adipocytes, fibrocytes, and sweat gland cells. Immunohistochemistry and immunofluorescence staining revealed positive staining for ubiquitin and p62. The detailed pathological and genetic features of this NIID family provide a valuable contribution to the existing knowledge base of this rare disorder.

Neuronal intranuclear inclusion disease: Two cases of dopa-responsive juvenile parkinsonism with drug-induced dyskinesia

2010 ◽  
Vol 25 (9) ◽  
pp. 1274-1279 ◽  
Author(s):  
Szu-Chia Lai ◽  
Shih-Ming Jung ◽  
Padraic Grattan-Smith ◽  
Ella Sugo ◽  
Yen-Wen Lin ◽  
...  
Keyword(s):  
Intranuclear Inclusion ◽  
Drug Induced ◽  
Juvenile Parkinsonism ◽  
Neuronal Intranuclear Inclusion

scholarly journals Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Atsuhiko Sugiyama ◽  
Takahiro Takeda ◽  
Mizuho Koide ◽  
Hajime Yokota ◽  
Hiroki Mukai ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Repeat Expansion ◽  
Cerebellar Hemisphere ◽  
Intranuclear Inclusions ◽  
Intranuclear Inclusion ◽  
Neuronal Intranuclear Inclusion ◽  
Lateral Sclerosis

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS. Case presentation A 60-year-old Taiwanese woman reported a four-month history of progressive weakness beginning in the right foot that spread to all four extremities. She was diagnosed with ALS because she met the revised El Escorial diagnostic criteria for definite ALS with upper and lower motor neuron involvement in the cervical, thoracic, and lumbosacral regions. She died of respiratory failure at 22 months from ALS onset, at the age of 62 years. Brain magnetic resonance imaging (MRI) revealed lesions in the medial part of the cerebellar hemisphere, right beside the vermis (paravermal lesions). The subclinical neuropathy, indicated by a nerve conduction study (NCS), prompted a potential diagnosis of NIID. Antemortem skin biopsy and autopsy confirmed the coexistence of pathology consistent with both ALS and NIID. We observed neither eccentric distribution of p62-positive intranuclear inclusions in the areas with abundant large motor neurons nor cytopathological coexistence of ALS and NIID pathology in motor neurons. This finding suggested that ALS and NIID developed independently in this patient. Conclusions We describe a case of concurrent NIID and ALS discovered during an autopsy. Abnormal brain MRI findings, including paravermal lesions, could indicate the coexistence of NIID even in patients with ALS showing characteristic clinical phenotypes.

scholarly journals Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-yi Kuai ◽  
Xiao-han Yao ◽  
Li-juan Xu ◽  
Yu-qing Zhou ◽  
Li-ping Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Neurodegenerative Disorder ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Motor Symptoms ◽  
Gastrointestinal Dysfunction ◽  
Before And After ◽  
Non Motor Symptoms

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

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